title: Modulation of COX, LOX and NFκB activities by Xanthium spinosum L. root extract and ziniolide.
abstract: Xanthium spinosum L. (Asteraceae) is a medicinal weed distributed worldwide. Many of its diverse ethnopharmacological uses - namely diarrhoea, inflammation, liver disorders, snake bite and fever - are linked - at least in part - to an uncontrolled release of arachidonic acid metabolites. The crude extract of X. spinosum roots from Jordanian origin dose-dependently inhibited the 5-LOX (IC50 is approximately equal to 10 μg/mL), COX-1(IC50 is approximately equal to 50 μg/mL), and 12-LOX (IC50 is approximately equal to 170 μg/mL) enzymatic pathways in intact pro-inflammatory cells. A direct activity at the level of PLA2 is not probable, but the extract induced the synthesis of the anti-inflammatory eicosanoid 15(S)-HETE, which may in turn inhibit this enzyme. 5-LOX bioguided fractionation of the crude extract led to the isolation of ziniolide, a known 12,8-guaianolide sesquiterpene lactone, from the hydro-alcoholic fraction of the n-hexane extract (IC50=69 μM). Both the plant extract and ziniolide are in vitro inhibitors of the phorbol-induced NFκB activation, a key regulator of the arachidonic pathway.
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia.
authors.forename: Ammar
authors.initials: A
authors.lastname: Bader
authors.affiliation: Departament de Farmacologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andrés Estellés, s/n. 46100 Burjassot, València, Spain.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Giner
authors.affiliation: Departament de Farmacologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andrés Estellés, s/n. 46100 Burjassot, València, Spain.
authors.forename: Francesca
authors.initials: F
authors.lastname: Martini
authors.affiliation: Departament de Farmacologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andrés Estellés, s/n. 46100 Burjassot, València, Spain; Cátedra de Farmacología Básica, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, CIC Provincia de Buenos Aires, La Plata, Buenos Aires, Argentina.
authors.forename: Guillermo R
authors.initials: GR
authors.lastname: Schinella
authors.affiliation: Departament de Farmacologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andrés Estellés, s/n. 46100 Burjassot, València, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Ríos
authors.affiliation: Dipartimento di Farmacia, Universita di Pisa, Via Bonanno 33, 56126 Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Braca
authors.affiliation: Departament de Farmacologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andrés Estellés, s/n. 46100 Burjassot, València, Spain; Centre for Pharmacognosy and Phytotherapy, University College London School of Pharmacy, 29-39 Brunswick Square, WC1N 1AX London, United Kingdom. Electronic address: j.prieto@ucl.ac.uk.
authors.forename: José M
authors.initials: JM
authors.lastname: Prieto
mesh_terms: D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D016859:Lipoxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D058945:Lipoxygenases / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010704:Phorbols; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D045789:Sesquiterpenes, Guaiane / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D031210:Xanthium / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D016328:NF-kappa B; D010704:Phorbols; D010936:Plant Extracts; D045789:Sesquiterpenes, Guaiane; C000588656:ziniolide; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D058945:Lipoxygenases; D051545:Cyclooxygenase 1; C033085:phorbol
keywords: Cyclooxygenase; Lipoxygenases; NF-κB; Sesquiterpene lactones; Xanthium spinosum; Ziniolide